Absence of AVPR2 copy number variation in eunatremic and dysnatremic subjects in non-Hispanic Caucasian populations

Yi Fu, Zhan Chen, Alexandra I F Blakemore, Eric Orwoll, David Cohen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Copy number variation (CNV) is increasingly recognized as a source of phenotypic variation among humans. We hypothesized that a CNV in the human arginine vasopressin receptor-2 gene (AVPR2) would be associated with serum sodium concentration based on the following lines of evidence: 1) the protein product of the AVPR2 gene is essential for renal water conservation; 2) mutations in the AVPR2 gene are associated with aberrant water balance in humans; 3) heritability of serum sodium concentration may be greater in females than in males; 4) the AVPR2 gene is X-linked; and 5) a common CNV spanning the AVPR2 gene was recently described in a non-Hispanic Caucasian population. We developed a highly reproducible assay for AVPR2 CNV. Among 279 subjects with measured serum sodium concentration in the Offspring Cohort of the Framingham Heart Study, no subjects exhibited CNV at the AVPR2 locus. Among 517 subjects in the Osteoporotic Fractures in Men Study (MrOS) - including 152 with hyponatremia and 183 with hypernatremia - no subjects with CNV at the AVPR2 locus were identified. CNV at the AVPR2 locus could not be independently confirmed, and CNV at the AVPR2 gene is unlikely to influence systemic water balance on a population-wide basis in non-Hispanic Caucasian subjects. A novel AVPR2 single nucleotide polymorphism affecting the reporter hybridization site gave rise to an artifactually low copy number signal (i.e., less than unity) in one male African American subject. Reanalysis of the original comparative genomic hybridization data revealed bona fide CNVs flanking - but not incorporating - the AVPR2 gene, consistent with our new genotyping data.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalPhysiological Genomics
Volume40
Issue number3
DOIs
StatePublished - Feb 2010

Fingerprint

Vasopressin Receptors
Gene Dosage
Population
Genes
Sodium
Water
Serum
Hypernatremia
X-Linked Genes
Osteoporotic Fractures
Comparative Genomic Hybridization
Hyponatremia
Essential Genes

Keywords

  • Arginine vasopressin
  • Hypernatremia
  • Hyponatremia
  • Osmoregulation

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Absence of AVPR2 copy number variation in eunatremic and dysnatremic subjects in non-Hispanic Caucasian populations. / Fu, Yi; Chen, Zhan; Blakemore, Alexandra I F; Orwoll, Eric; Cohen, David.

In: Physiological Genomics, Vol. 40, No. 3, 02.2010, p. 121-127.

Research output: Contribution to journalArticle

@article{b69d7d281f6a4aecbce307986b5af2da,
title = "Absence of AVPR2 copy number variation in eunatremic and dysnatremic subjects in non-Hispanic Caucasian populations",
abstract = "Copy number variation (CNV) is increasingly recognized as a source of phenotypic variation among humans. We hypothesized that a CNV in the human arginine vasopressin receptor-2 gene (AVPR2) would be associated with serum sodium concentration based on the following lines of evidence: 1) the protein product of the AVPR2 gene is essential for renal water conservation; 2) mutations in the AVPR2 gene are associated with aberrant water balance in humans; 3) heritability of serum sodium concentration may be greater in females than in males; 4) the AVPR2 gene is X-linked; and 5) a common CNV spanning the AVPR2 gene was recently described in a non-Hispanic Caucasian population. We developed a highly reproducible assay for AVPR2 CNV. Among 279 subjects with measured serum sodium concentration in the Offspring Cohort of the Framingham Heart Study, no subjects exhibited CNV at the AVPR2 locus. Among 517 subjects in the Osteoporotic Fractures in Men Study (MrOS) - including 152 with hyponatremia and 183 with hypernatremia - no subjects with CNV at the AVPR2 locus were identified. CNV at the AVPR2 locus could not be independently confirmed, and CNV at the AVPR2 gene is unlikely to influence systemic water balance on a population-wide basis in non-Hispanic Caucasian subjects. A novel AVPR2 single nucleotide polymorphism affecting the reporter hybridization site gave rise to an artifactually low copy number signal (i.e., less than unity) in one male African American subject. Reanalysis of the original comparative genomic hybridization data revealed bona fide CNVs flanking - but not incorporating - the AVPR2 gene, consistent with our new genotyping data.",
keywords = "Arginine vasopressin, Hypernatremia, Hyponatremia, Osmoregulation",
author = "Yi Fu and Zhan Chen and Blakemore, {Alexandra I F} and Eric Orwoll and David Cohen",
year = "2010",
month = "2",
doi = "10.1152/physiolgenomics.00157.2009",
language = "English (US)",
volume = "40",
pages = "121--127",
journal = "Physiological Genomics",
issn = "1094-8341",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Absence of AVPR2 copy number variation in eunatremic and dysnatremic subjects in non-Hispanic Caucasian populations

AU - Fu, Yi

AU - Chen, Zhan

AU - Blakemore, Alexandra I F

AU - Orwoll, Eric

AU - Cohen, David

PY - 2010/2

Y1 - 2010/2

N2 - Copy number variation (CNV) is increasingly recognized as a source of phenotypic variation among humans. We hypothesized that a CNV in the human arginine vasopressin receptor-2 gene (AVPR2) would be associated with serum sodium concentration based on the following lines of evidence: 1) the protein product of the AVPR2 gene is essential for renal water conservation; 2) mutations in the AVPR2 gene are associated with aberrant water balance in humans; 3) heritability of serum sodium concentration may be greater in females than in males; 4) the AVPR2 gene is X-linked; and 5) a common CNV spanning the AVPR2 gene was recently described in a non-Hispanic Caucasian population. We developed a highly reproducible assay for AVPR2 CNV. Among 279 subjects with measured serum sodium concentration in the Offspring Cohort of the Framingham Heart Study, no subjects exhibited CNV at the AVPR2 locus. Among 517 subjects in the Osteoporotic Fractures in Men Study (MrOS) - including 152 with hyponatremia and 183 with hypernatremia - no subjects with CNV at the AVPR2 locus were identified. CNV at the AVPR2 locus could not be independently confirmed, and CNV at the AVPR2 gene is unlikely to influence systemic water balance on a population-wide basis in non-Hispanic Caucasian subjects. A novel AVPR2 single nucleotide polymorphism affecting the reporter hybridization site gave rise to an artifactually low copy number signal (i.e., less than unity) in one male African American subject. Reanalysis of the original comparative genomic hybridization data revealed bona fide CNVs flanking - but not incorporating - the AVPR2 gene, consistent with our new genotyping data.

AB - Copy number variation (CNV) is increasingly recognized as a source of phenotypic variation among humans. We hypothesized that a CNV in the human arginine vasopressin receptor-2 gene (AVPR2) would be associated with serum sodium concentration based on the following lines of evidence: 1) the protein product of the AVPR2 gene is essential for renal water conservation; 2) mutations in the AVPR2 gene are associated with aberrant water balance in humans; 3) heritability of serum sodium concentration may be greater in females than in males; 4) the AVPR2 gene is X-linked; and 5) a common CNV spanning the AVPR2 gene was recently described in a non-Hispanic Caucasian population. We developed a highly reproducible assay for AVPR2 CNV. Among 279 subjects with measured serum sodium concentration in the Offspring Cohort of the Framingham Heart Study, no subjects exhibited CNV at the AVPR2 locus. Among 517 subjects in the Osteoporotic Fractures in Men Study (MrOS) - including 152 with hyponatremia and 183 with hypernatremia - no subjects with CNV at the AVPR2 locus were identified. CNV at the AVPR2 locus could not be independently confirmed, and CNV at the AVPR2 gene is unlikely to influence systemic water balance on a population-wide basis in non-Hispanic Caucasian subjects. A novel AVPR2 single nucleotide polymorphism affecting the reporter hybridization site gave rise to an artifactually low copy number signal (i.e., less than unity) in one male African American subject. Reanalysis of the original comparative genomic hybridization data revealed bona fide CNVs flanking - but not incorporating - the AVPR2 gene, consistent with our new genotyping data.

KW - Arginine vasopressin

KW - Hypernatremia

KW - Hyponatremia

KW - Osmoregulation

UR - http://www.scopus.com/inward/record.url?scp=76549118312&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76549118312&partnerID=8YFLogxK

U2 - 10.1152/physiolgenomics.00157.2009

DO - 10.1152/physiolgenomics.00157.2009

M3 - Article

C2 - 19996159

AN - SCOPUS:76549118312

VL - 40

SP - 121

EP - 127

JO - Physiological Genomics

JF - Physiological Genomics

SN - 1094-8341

IS - 3

ER -